This study will analyze the sequence of changes in ultrastructure and in subcellular electrolyte content occurring in animal hearts subjected to chronic pressure or volume work overload that produces cardiac hypertrophy. It will also correlate these changes with alterations in the regional distribution of myocardial blood flow. Pressure overloading will be induced by aortic banding with a cuff, and volume overloading will be caused by an arteriovenous fistula regulated by a cuff. These work overloads will be induced in chronically instrumented conscious dogs. Regional blood flows will be measured using radiolabeled tracer microsphere methods. We will study mechanisms of protein synthesis with high resolution autoradiography to determine whether previously observed proliferation of Z-material in hypertrophied hearts represents degenerative or regenerative changes or both. X-ray microanalysis will determine the elemental composition of electron-dense deposits seen within the organelles of hypertrophied myocardium, defining subcellular electrolyte balance. We will also administer several cardiovascular drugs continuously, before and during chronic work overload, and evaluate their effects on ultrastructure, on subcellular electrolyte balance, and on regional distribution of myocardial blood flow. We will attempt to define the factors that characterize early irreversibility of cardiac hypertrophy. Better quantitative definitions may be clinically useful in judging which patients with valvular or congenital heart disease should be candidates for surgical intervention to restore normal myocardial function.